Immunostimulating guanosine derivatives and their pharmaceutical compositions

Abstract

7,8-Disubstituted guanosine nucleoside derivatives are found to be potent immune response enhancing agents in human and animal cells. 7-Substituents are heteroatom-substituted-hydrocarbyl radicals having a length greater than ethyl and less than about decyl. 8-Substituents are ═O, ═S, ═Se and ═NCN. Compositions and methods of use are also disclosed.

What is claimed is: 
     
       1. A substituted guanine nucleoside derivative that corresponds to the formula ##STR3## wherein X is O; R 1  is a heteroatom-substituted-hydrocarbyl radical selected from the group consisting of monohalosubstituted C 2  to C 8  alkyl, dihydroxy C 3  to C 6  alkyl, nitro substituted benzyl, C 1  to C 6  alkoxy substituted benzyl, and a C 1  to C 6  alkyl--O--(═O)--C 1  to C 5  alkylidene radical where the length of said radical is less than that of a decyl group;   R 2  and R 3  are the same or different radicals selected from the group consisting of hydrogen, hydroxyl, C 1  to C 6  alkoxy, lower alkanoyloxy, and benzoyloxy or R 2  and R 3  together constitute a C 1  to C 6  alkylidenedioxy radical;   R 4  is a radical selected from the group consisting of hydrogen, C 1  to C 6  alkanoyl, and benzoyl; and   the pharmaceutically acceptable, non-toxic base addition salts thereof.   
     
     
       2. The substituted guanine nucleoside derivative of claim 1 wherein said R 1  radical has a length less than heptyl. 
     
     
       3. The substituted guanine nucleoside of claim 1 wherein R 4  is hydrogen. 
     
     
       4. The substituted guanine nucleoside derivative of claim 1 wherein R 2  and R 3  are hydroxyl, and R 4  is hydrogen. 
     
     
       5. The substituted guanine nucleoside derivative of claim 1 wherein R 2  and R 3  are hydroxyl and R 4  is hydrogen. 
     
     
       6. 7-Carbethoxymethyl-8-oxoguanosine. 
     
     
       7. 7-(4-Nitrobenzyl)-8-oxoguanosine. 
     
     
       8. 8-(4-Methoxybenzyl)-8-oxoguanosine. 
     
     
       9. 7-(2-Chloroethyl)-8-oxoguanosine. 
     
     
       10. 7-(2,3-dihydroxypropyl)-8-oxoguanosine. 
     
     
       11. A pharmaceutical composition a diluent amount of a physiologically tolerable carrier admixed with a compound of claim 1. 
     
     
       12. The composition of claim 11 wherein said R 1  radical has a length less than heptyl. 
     
     
       13. The composition of claim 11 wherein R 2  and R 3  are hydroxyl, and R 4  is hydrogen.